In the trial, which is designed to compare the effect of two combined
endocrine therapy regimensthe GnRH analogue goserelin (Zoladex) plus tamoxifen
(Nolvadex) vs goserelin plus the aroma-tase inhibitor anastrozole (Arimidex)patients
who also received zoledronic acid (Zometa) avoided the reduction in bone
mineral density seen up to 6 months after treatment began. "Longer-term
monitoring will be necessary to determine whether these effects are prolonged,"
said Michael Gnant, MD, professor of surgery, University of Vienna, Austria.

The study is Trial 12 of the Austrian Breast & Colorectal Cancer Study Group
(ABCSG). It follows up on already published results suggesting that combined
goserelin and tamoxifen treatment is at least as effective as standard CMF (cyclophosphamide,
methotrexate, fluorouracil) chemotherapy as adjuvant treatment of
hormone-responsive breast cancer in premenopausal women.

The ABCSG Trial 12 will show whether goserelin/anastrozole can improve upon
the results already observed for goserelin/tamoxifen. "There are some data that
the estradiol suppression is even more effective with goserelin/anastro-zole,"
Dr. Gnant said.

Investigators have enrolled 1,250 women with stage I-II estrogen- or pro-gesterone-receptor-positive
disease and randomized them to goserelin (3.6 mg subcutaneously every 28 days)
plus oral tamoxifen (20 mg/d) or oral anastrozole (1 mg/d) for a total of 3
years.

As a secondary goal, investigators want to determine whether bisphosphonate
support can inhibit the detrimental effects of combination therapy on bone
mineral density; furthermore, adding a bisphosphonate may improve relapse-free
survival, Dr. Gnant said. Accordingly, half of each group received zoledronic
acid as an IV infusion every 6 months. "Initially we used a higher dose (6 mg)
of zoledronic acid," Dr. Gnant said. "However, due to safety concerns with
respect to renal function, the dose was reduced to 4 mg after the first 100
patients."

As of the San Antonio report, 278 out of a planned 667 patients had been
subjected to bone mineral density measurements of the lumbar spine and
trochanter femoris by standard densitometry. However, the preplanned interim
analysis reported by Dr. Gnant focused on the 172 women for whom three separate
measurements had been taken (baseline, 6 and 12 months after treatment).